In Drosophila, the bithorax gene complex (BX-C) is a giant cluster of genes that plays a major role in determing the body segmentation plan, especially of the thoracic and abdominal regions (Nature 276:565 570, 1978). Aims of the proposed work are to determine the mechanisms underlying cis- and trans-regulation of the complex and the nature and function of the substances produced by the genes of the complex. The specific model being tested by a combination of genetic and cytological techniques coupled with molecular approaches (the latter in a collaborative effort) is that in the wild-type organism the more posterior the segment the more genes of the complex become derepressed. Genes once derepressed in a given segment tend to be derepressed in all segments posterior thereto. The more proximal a gene is in the complex the more likely (with one exception) it is to be derepressed. Two gradients are invoked to explain the wild-type pattern: a gradient along the embryo in the Pc+ substance and a gradient along the chromosome in the affinity of the cis-regulatory elements for that substance. The long-term objective is to understand the genetic and molecular basis of a developmental pathway of a eukaryotic organism. The health significance is that the human embryo is expected to use similar sets of master regulatory genes to control the differentiation of the head, thoracic and abdominal regions of the body. Defects in such genes would be responsible for many types of congenial abnormalities. By eventually identifying such gene clusters at the molecular level, certain kinds of congenital abnormalities may eventually be corrected or alleviated.